COREGULATION OF 2 EMBEDDED GENE-PRODUCTS, CHOLINE-ACETYLTRANSFERASE AND THE VESICULAR ACETYLCHOLINE TRANSPORTER

The gene encoding the vesicular acetylcholine transporter (VAChT) has recently been localized within the first intron of the gene encoding c holine acetyltransferase (ChAT) and is in the same transcriptional ori entation. These two genes, whose products are required for the express ion of the cholinergic phenotype, could therefore be coregulated. We t hus tested the effects on VAChT gene expression of the cholinergic dif ferentiation factor/leukemia inhibitory factor and retinoic acid, both of which induce ChAT activity and increase ChAT mRNA levels in cultur ed sympathetic neurons. These factors increased both the number of bin ding sites for vesamicol, a specific ligand of VAChT, and VAChT immuno reactivity. This increase in the number of VAChT molecules resulted fr om an increase in the amount of VAChT mRNA, as assessed by reverse tra nscription-PCR and which paralleled that of ChAT mRNAs. These data sug gest a functional role for ChAT and VAChT gene organization and are co nsistent with the existence of a coregulatory mechanism for the embedd ed ChAT and VAChT genes.